This application is for the second competing renewal of our interdisciplinary pre-doctoral training grant on The Molecular Pathogenesis of Infectious Diseases at the University of Colorado School of Medicine. This emerging area of investigation encompasses molecular biological and biochemical studies on microbial virulence determinants, host resistance mechanisms, regulation of transcription and translation during infection, structure-function analysis of microbial and host cell molecules that play key roles in infections, analysis of interactions of bacteria and viruses with differentiated host cells in vitro, and studis on bacterial and viral infections in animal models using either wild-type or genetically modified strains of microbes and host animals. The highly interactive members of our training faculty have proven productivity for innovative research in these areas, have secured research funding from NIH, NSF, DOD and other granting agencies, and accumulate years of experience in training pre-doctoral students in the multidisciplinary approaches needed for cutting-edge research on the pathogenesis of infectious diseases. In addition to performing their mentored research projects, our trainees will participate in a comprehensive program of didactic courses, seminars, journal clubs, and research-in-progress meetings that will train them to identify important new research questions, design well-controlled experiments using a wide variety of molecular, cellular and in vivo techniques, critically evaluate and present their results, and understand and apply principles of ethics to their research. Students are selected for appointment to this training program only after they have completed their required course work, passed their preliminary and comprehensive examinations and begun their dissertation research. The breadth of our integrated, interdepartmental training grant will prepare students for successful careers in academia and biotechnology. This dynamic training grant has been remarkably successful. It has fostered new research collaborations and grants among the training grant faculty, improved the curriculum, and fostered interdisciplinary interactions among the pre-doctoral trainees and trainers. In the five years since our training program on the Molecular Pathogenesis of Infectious Diseases was renewed in 2007, our training faculty increased from 21 to 24, and over 30 pre-doctoral trainees have populated at any given time the labs of training grant faculty for the past 8 years. In addition, the number of publications authored by our trainees grew from 29 in the 2002-2006 year period to 62 since 2007. We request four positions each year for the next five years to maintain the level of outstanding interdisciplinary training that our students receive in the multiple aspects of molecular pathogenesis of infectious diseases that are investigated in the laboratories of our training grant faculty.